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Journal ArticleDOI

Emerging roles of tRNA in adaptive translation, signalling dynamics and disease.

TLDR
In this article, emerging concepts regarding how tRNA abundance is dynamically regulated and how tRNAs (and their nucleolytic fragments) are centrally involved in stress signalling and adaptive translation, operating across a wide range of timescales.
Abstract
tRNAs, nexus molecules between mRNAs and proteins, have a central role in translation. Recent discoveries have revealed unprecedented complexity of tRNA biosynthesis, modification patterns, regulation and function. In this Review, we present emerging concepts regarding how tRNA abundance is dynamically regulated and how tRNAs (and their nucleolytic fragments) are centrally involved in stress signalling and adaptive translation, operating across a wide range of timescales. Mutations in tRNAs or in genes affecting tRNA biogenesis are also linked to complex human diseases with surprising heterogeneity in tissue vulnerability, and we highlight cell-specific aspects that modulate the disease penetrance of tRNA-based pathologies.

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Citations
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Journal ArticleDOI

Dynamic RNA Modifications in Gene Expression Regulation

TL;DR: Roles for mRNA modification in nearly every aspect of the mRNA life cycle, as well as in various cellular, developmental, and disease processes are revealed.
Journal ArticleDOI

RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation

TL;DR: The broad roles of m(6)A in regulating cell fates and embryonic development highlight the existence of another layer of epigenetic regulation at the RNA level, where mRNA is subjected to chemical modifications that affect protein expression.
Journal ArticleDOI

Efficient and quantitative high-throughput tRNA sequencing

TL;DR: Efficient and quantitative tRNA sequencing in HEK293T cells is achieved by using engineered demethylases to remove base methylations and a highly processive thermostable group II intron reverse transcriptase to overcome obstacles.
Journal ArticleDOI

Epigenetic inheritance of acquired traits through sperm RNAs and sperm RNA modifications

TL;DR: Insight is reviewed into the possible mechanisms by which sperm become acquisitive following environmental–somatic–germline interactions, and how they transmit paternally acquired phenotypes by shaping early embryonic development.
Journal ArticleDOI

Modulated Expression of Specific tRNAs Drives Gene Expression and Cancer Progression

TL;DR: A high-throughput tRNA profiling method finds that specific tRNAs are upregulated in human breast cancer cells as they gain metastatic activity, implicating tRNAGluUUC and tRNAArgCCG as promoters of breast cancer metastasis.
References
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Journal ArticleDOI

Surface Proteins of Gram-Positive Bacteria and Mechanisms of Their Targeting to the Cell Wall Envelope

TL;DR: The mechanisms for both sorting and targeting of proteins to the envelope of gram-positive bacteria are described and the functions of known surface proteins are reviewed.
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Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNALys mutation

TL;DR: An A to G transition mutation at nucleotide pair 8344 in human mitochondrial DNA has been identified as the cause of MERRF, providing molecular confirmation that some forms of epilepsy are the result of deficiencies in mitochondrial energy production.
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Translational control in stress and apoptosis

TL;DR: Two representative models are examined, the regulation of eukaryotic initiation factor-2α by phosphorylation and internal ribosome initiation through the internal Ribosome-entry site, which illustrate the importance of translational control in the cellular stress response and apoptosis.
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Synonymous but not the same: the causes and consequences of codon bias.

TL;DR: Ongoing work to quantify the dynamics of initiation and elongation is as important for understanding natural synonymous variation as it is for designing transgenes in applied contexts.
Journal ArticleDOI

Aminoacyl-tRNA synthesis.

TL;DR: Current knowledge of the biochemical, structural, and evolutionary facets of aminoacyl-tRNA synthesis is reviewed, mainly prompted by the advent of whole genome sequencing and the availability of vast body of structural data.
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